Acute ischemic syndromes like unstable angina or myocardial infarction are often triggered by physical exercise or mental stress. We wanted to study the effect of exercise and mental stress on platelet activation in patients with coronary artery disease. We use a technique called impedance aggregometry that measures platelet function on blood collected upstream and downstream from the coronary circulation. The study took place in the catheterization laboratory. We measured platelet function at rest and in response to speeding up the heart rate to mimic exercise and also after a three-minute period of mental stress, while the patient was playing a video game during his catheterization. We also measured platelet function while the patient was exercising with a bicycle algometer during his catheterization. We have shown in the past and confirmed in this study, that in patients with significant narrowing of their coronary arteries platelet response to speeding heart rate by increasing their tendency to form clots. In this study we show that mental stress causes a more generalized activation of platelets. We also show that physical exercise also produces a generalized activation of platelets. And, finally, we showed that nitroglycerin, sodium nitroprusside infusion or aspirin all reduced platelet activation in response to rapid atrial pacing. In conclusion, increase in coronary flow induced by speeding up the heart, induces platelet activation in the coronary circulation that could be blunted by nitroglycerin, nitroprusside or aspirin. In contrast mental stress or exercise produce a more system activation, probably due to an increase in catecholamines. These mechanisms may play a role in the precipitation of acute ischemic syndromes in patients with stable coronary artery disease.